Jasmonates induce Arabidopsis bioactivities selectively inhibiting the growth of breast cancer cells through CDC6 and mTOR.
Jasmonates induce Arabidopsis bioactivities selectively inhibiting the growth of breast cancer cells through CDC6 and mTOR.
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茉莉酸通过CDC6和mTOR诱导拟南芥生物活性，选择性地抑制乳腺癌细胞的生长。
DOI：
10.1111/nph.17031
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发表时间：
2021-03
期刊：
影响因子：
--
通讯作者：
Devoto A
中科院分区：
文献类型：
--
作者：
Bömer M;Pérez-Salamó I;Florance HV;Salmon D;Dudenhoffer JH;Finch P;Cinar A;Smirnoff N;Harvey A;Devoto A
植物化学物质经常在体外和体内用于癌症研究。植物激素茉莉酸酯(Jas)通过复杂的调控网络控制特定代谢物的合成。JAS在癌细胞和正常细胞混合群体中具有选择性细胞毒作用。在这里，将非药用植物拟南芥的叶片外植体与人乳腺癌细胞直接孵育，选择性地抑制癌细胞的生长。高通量LC-MS鉴定了拟南芥的代谢产物。检测乳腺癌细胞中细胞周期调节蛋白和转录水平。茉莉酸甲酯(MeJA)和甲基茉莉酸甲酯(MeJA)处理的拟南芥叶片代谢物上调对乳腺癌细胞周期的协同作用与细胞分裂周期6(CDC6)、细胞周期蛋白依赖性激酶2(CDK2)、细胞周期蛋白D1和D3有关，表明关键的细胞周期成分介导了细胞活力的降低。吲哚类、喹啉类和顺-(+)-12-氧代植物二烯酸等生物活性物质在协同作用下可作为抗癌化合物。我们的工作表明，MeJA治疗在改变DNA复制调节因子CDC6方面具有普遍作用，通过雷帕霉素、mTOR和Jas的机制靶点之间的串扰，支持跨王国保守细胞周期调节。这项研究对从没有已知药用谱系的植物中鉴定具有抗癌生物活性的代谢物具有重要意义，并将在疾病治疗的开发中应用。
Phytochemicals are used often in vitro and in vivo in cancer research. The plant hormones jasmonates (JAs) control the synthesis of specialized metabolites through complex regulatory networks. JAs possess selective cytotoxicity in mixed populations of cancer and normal cells. Here, direct incubation of leaf explants from the non‐medicinal plant Arabidopsis thaliana with human breast cancer cells, selectively suppresses cancer cell growth. High‐throughput LC‐MS identified Arabidopsis metabolites. Protein and transcript levels of cell cycle regulators were examined in breast cancer cells. A synergistic effect by methyljasmonate (MeJA) and by compounds upregulated in the metabolome of MeJA‐treated Arabidopsis leaves, on the breast cancer cell cycle, is associated with Cell Division Cycle 6 (CDC6), Cyclin‐dependent kinase 2 (CDK2), Cyclins D1 and D3, indicating that key cell cycle components mediate cell viability reduction. Bioactives such as indoles, quinolines and cis‐(+)‐12‐oxophytodienoic acid, in synergy, could act as anticancer compounds. Our work suggests a universal role for MeJA‐treatment of Arabidopsis in altering the DNA replication regulator CDC6, supporting conservation, across kingdoms, of cell cycle regulation, through the crosstalk between the mechanistic target of rapamycin, mTOR and JAs. This study has important implications for the identification of metabolites with anti‐cancer bioactivities in plants with no known medicinal pedigree and it will have applications in developing disease treatments
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影响因子：
16
作者：
Chuang, Li-Chiou;Teixeira, Leonardo K.;Wohlschlegel, James A.;Henze, Martha;Yates, John R.;Mendez, Juan;Reed, Steven I.
通讯作者：
Reed, Steven I.
影响因子：
7.2
作者：
Devoto, A;Nieto-Rostro, M;Turner, JG
通讯作者：
Turner, JG
影响因子：
5.1
作者：
Devoto, A;Ellis, C;Turner, JG
通讯作者：
Turner, JG
影响因子：
6.2
作者：
Abukhdeir AM;Park BH
通讯作者：
Park BH
影响因子：
11.4
作者：
Fingrut, O;Flescher, E
通讯作者：
Flescher, E